Clinical prediction rules for mortality in patients with pulmonary embolism and cancer to guide outpatient management: a meta-analysis.

Essentials Clinical prediction rules (CPRs) can stratify patients with pulmonary embolism (PE) and cancer. A meta-analysis was done to assess prognostic accuracy in CPRs for mortality in these patients. Eight studies evaluating ten CPRs were included in this study. CPRs should continue to be used with other patient factors for mortality risk stratification. SUMMARY: Background Cancer treatment is commonly complicated by pulmonary embolism (PE), which remains a leading cause of morbidity and mortality in these patients. Some guidelines recommend the use of clinical prediction rules (CPRs) to help clinicians identify patients at low risk of mortality and therefore guide care. Objective To determine and compare the accuracy of available CPRs for identifying cancer patients with PE at low risk of mortality. Methods A literature search of Medline and Scopus (January 2000 to August 2017) was performed. Studies deriving/validating ≥ 1 CPR for early post-PE all-cause mortality were included. A bivariate, random-effects model was used to pool sensitivity and specificity estimates for each CPR. Traditional random-effects meta-analysis was performed to estimate the weighted proportion of patients deemed at low risk of early mortality, mortality in low risk patients and odds ratios for death compared with higher-risk patients. Results Eight studies evaluating 10 CPRs were included. The highest sensitivities were observed with Hestia (98.1%, 95% confidence interval [CI] = 75.6-99.9%) and the EPIPHANY index (97.4%, 95% CI = 93.2-99.0%); sensitivities of remaining rules ranged from 59.9 to 96.6%. Of the six CPRs with sensitivities ≥ 95%, none had specificities > 33%. Random-effects meta-analysis suggested that 6.6-51.6% of cancer patients with PE were at low risk of mortality, 0-14.3% of low-risk patients died and low-risk patients had a 43-94% lower odds of death compared with those at higher risk. Conclusions Because of the limited total body of evidence regarding CPRs, their results, in conjunction with other pertinent patient-specific clinical factors, should continue to be used in identifying appropriate management for PE in patients with cancer.

Systematic review of the cost-effectiveness of varenicline vs. bupropion for smoking cessation.

The purpose of this systematic review was to review the cost-effectiveness of first-line non-nicotine therapies (varenicline and bupropion SR) for smoking cessation, identify differences in the models used and their conclusions of cost-effectiveness, and to determine which variables, if any, impact conclusions of cost-effectiveness. A systematic literature search was conducted in MEDLINE, PsychINFO, the National Health Service Economic Evaluation Database, the Health Technology Database and the Tufts Cost-effectiveness Analysis Registry from the earliest possible date through May 2011. To be included, studies had to compare cost-effectiveness of varenicline to bupropion using either a Markov model or discrete event simulation and be published as a full text manuscript in English or Spanish. Study selection and data extraction were done in duplicate with disagreement resolved through discussion. Data regarding the model characteristics, results and conclusions were extracted as were details to assess the quality of the study. Model characteristics and cost-effectiveness results were compared across studies and summarised qualitatively. Ten unique studies were included, all of which were Markov models. Eight studies used the Benefits of Smoking Cessation on Outcomes (BENESCO) model and all found varenicline to dominate bupropion. The two non-BENESCO models found varenicline to be cost-effective. Conclusions regarding the cost-effectives were changed upon sensitivity analysis with the following variables: time horizon, cost of bupropion, efficacy of either drug, age and the incidence of smoking related disease. Varenicline dominated bupropion in most cost-effectiveness models. However, applicability of models to clinical practice and variables which changed conclusion of cost-effectiveness should be considered in the interpretation of results.

Are the risk factors listed in warfarin prescribing information associated with anticoagulation-related bleeding? A systematic literature review.

Warfarin significantly reduces thromboembolic risk, but perceptions of associated bleeding risk limit its use. The evidence supporting the association between bleeding and individual patient risks factors is unclear. This systematic review aims to determine the strength of evidence supporting an accentuated bleeding risk when patients with risk factors listed in the warfarin prescribing information are prescribed the drug. A systematic literature search of MEDLINE and Cochrane CENTRAL was conducted to identify studies reporting multivariate relationships between prespecified covariates and the risk of bleeding in patients receiving warfarin. The prespecified covariates were identified based on patient characteristics for bleeding listed in the warfarin package insert. Each covariate was evaluated for its association with specific types of bleeding. The quality of individual evaluations was rated as 'good', 'fair' or 'poor' using methods consistent with those recommended by the Agency for Healthcare Research and Quality (AHRQ). Overall strength of evidence was determined using the Grading of Recommendations Assessment, Development (GRADE) criteria and categorised as 'insufficient', 'very low', 'low', 'moderate' or 'high'. Thirty-four studies, reporting 134 multivariate evaluations of the association between a covariate and bleeding risk were identified. The majority of evaluations had a low strength of evidence for the association between covariates and bleeding and none had a high strength of evidence. Malignancy and renal insufficiency were the only two covariates that had a moderate strength of evidence for their association with major and minor bleeding respectively. The associations between covariates listed in the warfarin prescribing information and increased bleeding risk are not well supported by the medical literature.